GLOMERULAR FILTERATION RATE

(GFR)
and
RENAL BLOOD FLOW

Dr. Akin Olanipekun

 GLOMERULAR FILTERATION
• It is the first step in urine formation.
• Glomerular filtration is the transfer of fluid and solutes from the glomerular
capillaries along a pressure gradient into Bowman's capsule.
• The ultrafilterate is essentially cell-free and protein-free and contains
crystalloids in virtually the same concentrations as in the plasma.
• Filteration occurs in the glomerulus due to
1. Filtration membrane:The wall of glomerular capillaries consists of
endothelial cells resting on a basement membrane and surrounded by
epithelial cells of Bowman capsule
2. Three physical forces: Capillary hydrostatic pressure, Colloid osmotic
pressure, Capsular hydrostatic pressure
 Glomerular Capillary Filtration Barrier
Each layer in the filtration membrane has a
special characteristic:
1. The endothelial cells of glomerular
capillaries are fenestrated ( 70-90 nm in
diameter).
2. The basement membrane: Containing
negatively charged glycoproteins. Act to
repel negatively charged plasma
proteins.
3. The epithelial cells of Bowman's
capsule have foot processes called
podocytes ( to form filtration slits a long
the capillary wall)
 GLOMERULAR FILTERATION RATE

• GFR is the volume of plasma filtered from both kidneys per minute.
• The GFR is the measurement of the kidneys ability to filter plasma.
• Normal GFR= 125ml/min ( 7.5L/h or 180L/d) in average adult male.
• GFR can be measured in intact experimental animals and humans by
measuring the plasma level of a substance and the amount of that substance
that is excreted.
Determinants of GFR
The GFR is determined by: NFP = forces favoring filtration - forces
1. The sum of the hydrostatic and opposing filtration
colloid osmotic forces across the
glomerular membrane, which
gives the net filtration pressure,
and
2. The glomerular filteration
coefficient-Kf (Depends on
permeability & effective surface
area)

Expressed mathematically, the GFR

= Kf x net filtration pressure(NFP)
Net Filteration Pressure
• The total force favoring filtration is
the glomerular capillary hydrostatic
pressure at 60 mm Hg.
• The total of the two forces opposing
filtration is 50 mm Hg.
• The net difference favoring filtration
(10 mm Hg of pressure) is called the
net filtration pressure.
• This modest pressure forces large
volumes of fluid from the blood
through the highly permeable
glomerular membrane.
Factors Affecting GFR
1. Increased Glomerular Capillary
Filteration Coeficient(Kf) increases GFR
2. Increased Bowman’s capsule hydrostatic
pressure(PB) decreases GFR
3. Increased Glomerular capillary colloidal
osmotic pressure(₶G) decreases GFR
4. Increased Glomerular capillary
hydrostatic pressure(PG) increases GFR
(determined by arterial pressure, afferent
arteriolar resistance, and efferent
arteriolar resistance)
 Measurement of GFR
Ideal substance used to measure GFR
must have the following characteristics:
1. Non toxic
2. Not metabolized, stored or produced
by the kidney
3. Freely filtered
4. Not reabsorbed by the renal tubules
5. Not secreted by the renal tubules.
• Examples of substances used to
measure the GFR: Inulin,
Creatinine, Iohexol, Radioisotopes
• Since the substance (X for
example) is not reabsorbed or
secreted by renal tubules:
• It’s Filtration = Excretion
• GFR x Px = Ux V
• Px= plasma concentration of x
• Ux = urine concentration of x
• V = urine flow rate (or urine volume
per unit time)
Note: This is the formula of
clearance
Renal Clearance
• Renal plasma clearance is the volume of plasma from which a substance is
completely removed by the kidney in a given amount of time (usually
minutes).
• Clearance of any substance(x) is measured by the formula Cx = Ux V/Px
It can be used for:
1. Measurement of GFR (by inulin or creatinine clearance).
2. Measurement of renal blood flow (by PAH clearance).
3. Assessment of renal function
 Measurement of GFR using inulin clearance
1. Inulin is given by continuous
intravenous infusion until its level in
plasma becomes constant.
2. A blood sample is taken to measure
its concentration in plasma (Px).
3. Urine is collected for 24 hours to
measure urine flow rate (V) and a
sample is taken to measure inulin
concentration in urine (Ux).
4. The formula of clearance is applied
to measure the GFR as follows:
GFR= UxV/Px.
 Measurement of GFR using creatinine clearance
1. Urine is collected for 24 hours to
measure urine flow rate (V).
2. A urine sample is taken to measure
creatinine concentration in urine (Ux).
3. A blood sample is taken to measure
creatinine concentration in plasma
(Px).
4. The formula of clearance is applied to
measure GFR (= UxV/Px).
• The disadvantage of creatinine is its
slight secretion by the proximal
convoluted tubules.
• This tends to give higher value for
GFR.
• However, the method used for
measuring creatinine in plasma gives
higher results.
• This corrects the error and gives
almost true GFR results.
 RENAL BLOOD FLOW

• In a resting adult, the combined blood flow through both kidneys is about
1200 ml/min, or about 22 percent of the cardiac output.
• Blood flow supplies the kidneys with nutrients and removes waste products.
• However, the high flow to the kidneys greatly exceeds this need.

• The purpose of this additional flow is to supply enough plasma for the high
rates of glomerular filtration that are necessary for precise regulation of body
fluid volumes and solute concentrations.
Renal blood vessels
Measurement of Renal Blood Flow
• The renal blood flow can be
measured using Fick principle.
• That is, by measuring the amount
of a given substance taken up per
unit of time and dividing this value
by the arteriovenous difference for
the substance across the kidney.
• Para-amino hippuric acid (PAH) is
used for measurement of the renal
blood flow.
Characterstics of PAH
1. Nontoxic & can be easily
measured in the blood & urine
2. Not affect the RBF & is not
metabolized, stored or produce by
the kidneys
3. Highly secreted to the extent that
its concentration in renal vein =
zero
 Clearance of PAH/RBF Meeasurement
ERPF =UPAH x V/ PPAH =Clearance of PAH
• Example:
• Concentration of PAH in urine
(UPAH)=14 mg/mL
• Urine flow (V˙)= 0.9 mL/min
• Concentration of PAH in plasma
(PPAH)= 0.02 mg/mL
• ERPF=14 × 0.9/0.02= 630 mL/min
• Average PAH extraction ratio: 0.9
• ERPF/Extraction ratio = Actual RPF
= 700 mL/min
• From the ARPF, the RBF can be
calculated by dividing by 1 minus
the hematocrit:
• Hematocrit (Hct): 45%
• RBF= ARPF/1-Hct
• = 700/1- 0.45 = 1273 mL/min
 Renal Oxygen Consumption
• Oxygen delivered to the kidneys far exceeds
their metabolic needs, and the arterial-venous
extraction of oxygen is relatively low compared
with that of most other tissues.
• Cortical blood flow is about 5 mL/g of kidney
tissue/min (compared with 0.5 mL/g/min in the
brain), and the arteriovenous oxygen difference
for the whole kidney is only 14 mL/L of blood,
compared with 62 mL/L for the brain and 114
mL/L for the heart.
• A large fraction of the oxygen consumed by the
kidneys is related to the high rate of active
sodium reabsorption by the renal tubules.
Hormonal/autacoid regulation of Renal Blood Flow

1. Norepinephrine constricts the renal vessels, with the greatest effect of

injected norepinephrine being exerted on the interlobular arteries and the
afferent arterioles.
2. Dopamine causes renal vasodilation and natriuresis.
3. Angiotensin II exerts a constrictor effect on both the afferent and efferent
arterioles.
4. Prostaglandins and bradykinins increase blood flow in the renal cortex and
decrease blood flow in the renal medulla.
5. Endothelial-Derived Nitric Oxide Decreases Renal Vascular Resistance and
Increases GFR.
6. Acetylcholine also produces renal vasodilation.
Assignment
• Write an essay on Autoregulation of Renal blood flow
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